Identification and functional expression of HAH1, a novel human gene involved in copper homeostasis

Leo W J Klomp, Su Ju Lin, Daniel S. Yuan, Richard D. Klausner, Valeria Cizewski Culotta, Jonathan D. Gitlin

Research output: Contribution to journalArticle

296 Citations (Scopus)

Abstract

To search for a mammalian homologue of ATX1, a human liver cDNA library was screened and a cDNA clone was isolated, which encodes a protein with 47% amino acid identity to Atx1p including conservation of the MTCXGC copper- binding domain. RNA blot analysis using this cDNA identified an abundant 0.5- kilobase mRNA in all human tissues and cell lines examined. Southern blot analysis using this same clone indicated that the corresponding gene exists as a single copy in the haploid genome, and chromosomal localization by fluorescence in situ hybridization detected this locus at the interface between bands 5q32 and 5q33. Yeast strains lacking copper/zinc superoxide dismutase (SOD1) are sensitive to redox cycling agents and dioxygen and are auxotrophic for lysine when grown in air, and expression of this human ATX1 homologue (HAH1) in these strains restored growth on lysine-deficient media. Yeast strains lacking ATX1 are deficient in high affinity iron uptake and expression of HAH1 in these strains permits growth on iron-depleted media and results in restoration of copper incorporation into newly synthesized Fet3p. These results identify HAH1 as a novel ubiquitously expressed protein, which may play an essential role in antioxidant defense and copper homeostasis in humans.

Original languageEnglish (US)
Pages (from-to)9221-9226
Number of pages6
JournalJournal of Biological Chemistry
Volume272
Issue number14
DOIs
StatePublished - Apr 4 1997
Externally publishedYes

Fingerprint

Copper
Homeostasis
Genes
Yeast
Lysine
Iron
Complementary DNA
Clone Cells
Yeasts
Haploidy
Growth
Southern Blotting
Fluorescence In Situ Hybridization
Gene Library
Liver
Restoration
Superoxide Dismutase
Oxidation-Reduction
Zinc
Conservation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Klomp, L. W. J., Lin, S. J., Yuan, D. S., Klausner, R. D., Culotta, V. C., & Gitlin, J. D. (1997). Identification and functional expression of HAH1, a novel human gene involved in copper homeostasis. Journal of Biological Chemistry, 272(14), 9221-9226. https://doi.org/10.1074/jbc.272.14.9221

Identification and functional expression of HAH1, a novel human gene involved in copper homeostasis. / Klomp, Leo W J; Lin, Su Ju; Yuan, Daniel S.; Klausner, Richard D.; Culotta, Valeria Cizewski; Gitlin, Jonathan D.

In: Journal of Biological Chemistry, Vol. 272, No. 14, 04.04.1997, p. 9221-9226.

Research output: Contribution to journalArticle

Klomp, LWJ, Lin, SJ, Yuan, DS, Klausner, RD, Culotta, VC & Gitlin, JD 1997, 'Identification and functional expression of HAH1, a novel human gene involved in copper homeostasis', Journal of Biological Chemistry, vol. 272, no. 14, pp. 9221-9226. https://doi.org/10.1074/jbc.272.14.9221
Klomp, Leo W J ; Lin, Su Ju ; Yuan, Daniel S. ; Klausner, Richard D. ; Culotta, Valeria Cizewski ; Gitlin, Jonathan D. / Identification and functional expression of HAH1, a novel human gene involved in copper homeostasis. In: Journal of Biological Chemistry. 1997 ; Vol. 272, No. 14. pp. 9221-9226.
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